Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients

Schoenberg, Markus Bo; Hao, Jihua; Bucher, Julian Nikolaus; Miksch, Rainer Christoph; Anger, H; Mayer, Barbara; Mayerle, Julia; Neumann, Jens; Guba, Markus; Werner, Jens; Bazhin, Alexandr V.

doi:10.3390/cancers10100389

Cited by 28 publications

(28 citation statements)

References 50 publications

(70 reference statements)

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“…Finally, we showed that the QTiS algorithm for different tumor types described previously [39,69] retrieved relevant results to highlight the importance of peritumoral TILs in patients with PDAC. Results with colorectal cancer indicate that quantification of immune cell infiltration has the potential to become an integral part of the TNM classification of PDAC [70].…”

Section: Discussionmentioning

confidence: 63%

Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer

Miksch

Schoenberg

Weniger

et al. 2019

Cancers

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In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3+, CD8+, and CD20+ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3+ TILs predicted progression after 12 months. The location of TILs’ hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

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Section: Discussionmentioning

confidence: 63%

Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer

Miksch

Schoenberg

Weniger

et al. 2019

Cancers

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“…Counting was done according to the QTiS algorithm by Miksch et al [48,49,50,51] with the ImageJ software (Version 1.51h, National Institutes of Health, Bethesda, MD, USA). Briefly, after substraction of background, color deconvolution was performed, selecting example regions for the following spectra: background, hematoxylin, and AEC.…”

Section: Methodsmentioning

confidence: 99%

Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer

Dötzer

Schlüter

Schoenberg

et al. 2019

Cancers

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CD3+ and CD8+ lymphocytes are well known prognostic markers in primary ovarian cancer. In contrast, the predictive value of the immune infiltrate concerning treatment response and the involvement of immune heterogeneity between primary and metastatic lesions are poorly understood. In this study, the immune infiltrate of 49 primary tumors and 38 corresponding lesions in the omentum (n = 23) and the peritoneum (n = 15) was immunohistochemically analyzed and correlated with clinicopathological factors and platinum-sensitivity. Immune heterogeneity was observed between paired primary and metastatic lesions for all immune cell phenotypes. The stromal immune infiltrate was higher in the omental lesions than in the primary tumors, which was reflected by CD45 (p = 0.007), CD3 (p = 0.005), CD8 (p = 0.012), and PD-1 (programmed cell-death protein 1) (p = 0.013). A higher stromal infiltrate of both CD45+ and CD3+ cells in the omental lesions was associated with the detection of lymph node metastasis (CD45, p = 0.018; CD3, p = 0.037). Platinum-sensitive ovarian cancers revealed a higher intratumoral CD8+ infiltrate in the peritoneal lesions compared to the primary tumors (p = 0.045). In contrast, higher counts of stromal PD-1+ cells in the peritoneal lesions have been associated with reduced platinum-sensitivity (p = 0.045). Immune heterogeneity was associated with platinum response and might represent a selection marker for personalized therapy.

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“…In the prognosis model of HCC, in terms of etiology, the prognostic model of hepatitis B correlated to HCC (PAGE-B, CU-HCC, GAG-HCC, and REACH-B for the development of HCC) must be established, 15,16 and in terms of treatment, it is more important to evaluate the prognosis of recurrence and survival after surgical resection. 17,18 However, in the whole HCC population, a tumor progression model for the evaluation of the clinical condition of patients with HCC is not available. In this study, we established a novel model for predicting HCC progression, and this model was compared with wellknown classic tumor models (TNM staging system,…”

Section: Discussionmentioning

confidence: 99%

<p>Use of a Novel Thyroid-Stimulating Hormone Model for Predicting the Progression of Hepatocellular Carcinoma</p>

Liu

Jiang

et al. 2020

OTT

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Background: Individuals with hepatocellular carcinoma (HCC) are at risk of tumor recurrence after surgical resection, which affects their survival. The aim of the present study was to establish a model for predicting tumor progression in patients with HCC. Methods: To develop and validate the efficacy of a novel prognostic model, a retrospective cohort with HCC (n = 1005) at Beijing Ditan Hospital was enrolled from January 2008 and June 2017. Furthermore, a prospective cohort (n = 77) was recruited to validate the association between thyroid-stimulating hormone (TSH) levels and tumor progression in patients with HCC. Results: The model used in predicting the progression of HCC included four variables (namely, Barcelona Clinic Liver Cancer [BCLC] stage, presence of portal vein tumor thrombus, alpha-fetoprotein level, and TSH level). The AUROC of the 1-year progressionfree survival (PFS) model was 0.755 and 0.753 in the deriving cohort and validation cohort, respectively, and these values were significantly higher than those of the Child-Pugh score, Model for End-stage Liver Disease (MELD), tumor-lymph node-metastasis (TNM) staging system, Okuda classification, and CLIP score. A simple assessment using a nomogram showed the 1-year PFS rate of patients with HCC. In the prospective cohort, the KM curve showed that the high TSH level group had a shorter PFS than the low TSH level (p = 0.001). Conclusion: The prognostic model of HCC progression was superior to other well-known classical tumor scoring systems. A high TSH level was correlated to poor outcome, particularly those with advanced HCC.

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Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients

Cited by 28 publications

References 50 publications

Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer

Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer

Immune Heterogeneity Between Primary Tumors and Corresponding Metastatic Lesions and Response to Platinum Therapy in Primary Ovarian Cancer

<p>Use of a Novel Thyroid-Stimulating Hormone Model for Predicting the Progression of Hepatocellular Carcinoma</p>

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